High-Risk Non-synonymous SNPs of Human Bcl-2 Gene Alters Structural Stability and Small Molecule Binding

High-Risk Non-synonymous SNPs of Human Bcl-2 Gene Alters Structural Stability and Small Molecule Binding

A. S. M. Zisanur Rahman, Arittra Bhattacharjee, Abdullah All Jaber, Maqsud Hossain, Kazi Nadim Hasan, Sohidul Islam and Zaied Ahmed Bhuyan

1Department of Biochemistry & Microbiology, North South University, Bashundhara,Dhaka- 1229, Bangladesh
2NSU Genome Research Institute, North South University, Bashundhara, Dhaka-1229, Bangladesh
3Department of Microbiology, University of Manitoba, Winnipeg, MB, Canada

ABSTRACT: B-cell lymphoma 2 (Bcl-2) gene, which encodes Bcl2 protein, is vital for apoptotic programmed cell death. In this study, computational approaches were performed to reveal the effect of non-synonymous single nucleotide polymorphisms (nsSNPs) in Bcl2 gene. A total of 79 nsSNPs were studied. Amongst all, 11 nsSNPs (M166T, G141E, R129C, S105P, F104S, R98L, L97P, H94P, V93A, G27S, V15L) were located at highly conserved region or functionally important domains with a high probability of being deleterious for Bcl-2 structure or role. Except for H94P, rest of the high-risk nsSNPs displayed decreased stability of BcL-2 structure. However, F104S attracted significant attention because it exhibited considerably reduced binding affinity than wild type Bcl-2 protein against HA 14-1 antagonist. This extensive computational experiment will assist as a valuable data source for upcoming population-based studies.

KEYWORDS: Bcl-2 gene, apoptosis, non-synonymous SNPs, HA 14-1

CORRESPONDENCE: Zaied Ahmed Bhuyan